Sickle cell disease (SCD) is a global health issue that affects ~100,000 Americans and over 13 million people worldwide. The complexity of the disease dictates that a multimodal approach to treatment will likely be needed. SCD is manifested physiologically during acute events of sickle crisis as the distorted red blood cells impede blood flow, causing physiological damage and severe pain. Generally characterized as a molecular disease, SCD exhibits many similarities with the pathophysiology of inflammation and reperfusion injury. As such, various forms of antioxidant therapies are being actively pursued as a new approach to treat SCD. No commercial therapeutic is available to treat or avert acute events of crisis, as the development has been stifled by the high (and toxic) concentration required for efficacy. Acute events are currently only managed with pain medication. Product and Long-Term Goal: Nanometics has developed a new type of multimodal therapeutic, termed AIC- 6020, as a small-molecule medication to be taken by patients at the onset or during sickle crisis. AIC-6020 directly modifies hemoglobin (HbS) to both inhibit sickling and to release a known antioxidant to help attenuate oxidative stress events in the microcirculation by antioxidant/anti-inflammatory mechanisms. AIC-6020 will be the first commercial therapeutic useful to treat acute events and the first multimodal therapeutic for SCD. Technical Innovation: Nanometics has developed a new class of multimodal therapeutics to treat sickle cell disease that incorporates two distinct therapeutic mechanisms into one chemical compound. The lead therapeutic reacts with HbS at stochiometric concentrations by a distinct transaldimination mechanism. Phase I Hypothesis and Specific Aims: The Phase I hypothesis was that AIC-6020 would be more effective and less toxic than 5-hydroxymethyl-2-furfural (5HMF). This hypothesis was successfully validated in vitro, ex vivo and in vivo (mice) where the efficacious concentration of AIC-6020 was >50% lower than that of 5HMF. Phase II Objectives: The Phase II objectives will be to 1) optimize the AIC approach to inhibit sickling at the lowest possible concentrations of AIC-6020, (2) establish the bioavailability of AIC-6020 and determine its toxicological and histopathological profile, and (3) examine the impact of AIC-6020 to attenuate events in the microcirculation that are etiologic to sickle cell disease. Commercial Opportunity: In the US alone, there are ~190,000 emergency room visits annually by patients seeking treatment for acute events of crisis, and ~42% of these visits required hospitalization for an average of 5 days. Additionally, there are ~300,000 babies born each year with sickle cell disease, and as infant death rates in developing countries decrease, the target market of patients is expected to rise dramatically over the next 20 years.